In children with suspected malaria do we need three negative blood films to exclude a diagnosis of Malaria?
– with thanks to Dr Tom Waterfield for summarising his recent article (5) below for Paediatric Pearls
There are over 300 new cases of imported paediatric malaria in the UK each year and cases of imported malaria here have been increasing over the last 20 years (1). Malaria in children is particularly difficult to diagnose because the initial presenting features are subtler than in adults. Children may appear quite well initially with a fever and no focus but; they are at risk of a rapid deterioration and are more likely to develop severe malaria.
The “gold standard” for ruling out the diagnosis of malaria if clinically suspected is three negative thin and thick blood films (2). This approach however, relies on serial phlebotomy and the availability of adequately trained staff. Furthermore, during out-of-hours periods the time and resources required are likely to result in delays in obtaining results especially if trained staff have to come in from home. There are now a range of Rapid Diagnostic Tests (RDTs) that are highly specific and sensitive for malaria. So are three films really required when we have RDTs?
There is only one study exploring the combination of blood films together with RDT’s in diagnosing imported malaria and it was in adults (3). Of the 388 cases, 367 (95%) were diagnosed by the initial blood film. Of the 21 that weren’t diagnosed on the blood film 19 had RDT’s performed. This diagnosed a further 10 leaving only 9 cases (2.3%) not picked up by a single blood film and RDT. Only one case of P.falciparum infection was missed and this was in a partially immune individual who had already received an unspecified treatment. The remaining 8 missed cases were P.vivax and P.ovale.
If we extrapolate from this study, then if a single blood film and RDT are negative a diagnosis of malaria is extremely unlikely. This is especially true in cases of suspected P.falciparum in a non-immune patient who has not received any treatment. The most obvious criticism here, is that it is difficult to extrapolate adult data and draw conclusions relating to children. However, the available data comparing parasite counts between children and adults suggests that on average children have a comparable or higher parasite count than adults (4). This would suggest that the results seen for adults would be comparable or even favourable in children.
Because of the paucity of data overall and lack of paediatric data it is not possible to make a blanket recommendation. The risk of malaria in each individual needs to be considered in conjunction with investigation results. For more information on diagnosing malaria in children read – How to interpret malaria tests (5).
References:
1. Ladhani S, Garbash M, Whitty CJ, Chiodini PL, Aibara RJ, Riordan FA, et al. Prospective, national clinical and epidemiologic study on imported childhood malaria in the United Kingdom and the Republic of Ireland. Pediatr Infect Dis J. 2010;29(5):434-8.
2. England PH. THE PHE MALARIA REFERENCE LABORATORYLABORATORY USER HANDBOOK. Public Health England2015.
3. Pasricha JM, Juneja S, Manitta J, Whitehead S, Maxwell E, Goh WK, et al. Is serial testing required to diagnose imported malaria in the era of rapid diagnostic tests? Am J Trop Med Hyg. 2013;88(1):20-3.
4. Mascarello M, Allegranzi B, Angheben A, Anselmi M, Concia E, Lagana S, et al. Imported malaria in adults and children: epidemiological and clinical characteristics of 380 consecutive cases observed in Verona, Italy. J Travel Med. 2008;15(4):229-36.
5. Dyer E, Waterfield T, Eisenhut M. How to interpret malaria tests. Arch Dis Child Educ Pract Ed. 2016 Apr;101(2):96-101. doi: 10.1136/archdischild-2015-309048. Epub 2016 Feb 2.